The ultimate goal of the proposed research is to elucidate the mechanism by which sensory inputs are translated into behavioral outputs. Using powerful genetic and imaging tools, we identified a novel population of olfactory sensory neurons (OSNs) in Drosophila that respond to CO2 and acidity. These neurons express an atypical olfactory receptor called IR64a that belongs to a family of divergent glutamate receptors, and can be directly stimulated by CO2 and acids as determined by a sensitive calcium imaging technique we developed. We identified a loss-of-function mutation of IR64a gene, and found that flies double mutant for IR64a and GR63a, the first CO2 receptor identified, have defective behavioral response to acids and high concentrations of CO2. The proposed study will dissect the role of these OSNs and their cognate receptor IR64a in mediating CO2 and acid avoidance behavior. We will determine whether IR64a+ neurons and IR64a gene are necessary and sufficient for mediating CO2 and acid sensation and avoidance. To characterize the function of the IR64a gene, we will analyze the physiological and behavioral phenotypes of IR64a mutant by calcium imaging and T-maze based behavioral assays. Furthermore, we will identify putative co-receptor subunits that interact with IR64a to mediate CO2 and acid sensation. The proposed study will provide insights into the underlying mechanisms of acid sensation and avoidance. Thus, these studies will help develop a foundation for furthering my interest in understanding the neuronal logic of avoidance behavior when I become an independent investigator. PUBLIC HEALTH RELEVANCE: The experiments described in this proposal will reveal the neural mechanism for sensing acidity through the olfactory system and address the function of a member of the novel ionotropic glutamate receptor family. Detailed knowledge of this receptor will provide insights into the function of other members of this family such as AMPAR and NMDA receptors, which have been implicated in many neurological diseases such as epilepsy, ischemic brain damage, and neurodegenerative disorders.